MAPPING OF A MAJOR OSTEOMAGENIC DETERMINANT OF MURINE LEUKEMIA-VIRUS RFB-14 TO NON-LONG TERMINAL REPEAT SEQUENCES

Certain isolates of murine leukemia viruses (MuLVs) have, apart from a leukemogenic potential, the capability of inducing diseases of nonhem atopoietic tissues in susceptible strains of mice. We have reported on the molecular cloning of a bone-tumorigenic virus, RFB-14 MuLV, which was found to induce benign bone tumors, osteomas, with 100% incidence in mice of the CBA/Ca strain (L. Pedersen, W. Behnisch, J. Schmidt, A . Luz, F. S. Pedersen, V. Erfle, and P. G. Strauss, J. Virol. 66:6186- 6190, 1992). In order to analyze the bone tumor-inducing phenotype of RFB-14 MuLV, we have studied the pathogenic potential of recombinant v iruses between RFB-14 and the nonosteomagenic, highly leukemogenic SL3 -3 MuLV. The recombinants were constructed so as to reveal whether a m ajor determinant of osteomagenicity maps to sequences within or outsid e the long terminal repeats (LTR). Our data show that a major determin ant of the osteoma-inducing potential of RFB-14 MuLV maps to the non-L TR region of the genome. Furthermore, we demonstrate that a strong det erminant of leukemogenicity is harbored by the non-LTR region of SL3-3 MuLV.